Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of NexoBrid in Children With Thermal Burns Compared the Standard of Care (NCT NCT02278718)

Last Updated: 2024-09-27

Results Overview

Measured by a survival analysis of incidence of complete eschar removal as a function of time. Eschar removal will be measured at the end of the debridement starting from randomization date, assessed until complete eschar removal is achieved (in days)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

145 participants

Primary outcome timeframe

From randomization date until complete eschar removal. For NexoBrid, assessed post application (post 2 h soaking) and for SOC assessed immediately post last dressing change for non-surgical SOC arm and immediately post excision for surgical SOC arm.

Results posted on

2024-09-27

Participant Flow

Out of 153 patients that were screened for enrollment, 145 patients were enrolled, randomized and included in FAS analysis. Seven patients were excluded at screening and one patient withdrew consent.

Participant milestones

Participant milestones
Measure	NexoBrid Gel NexoBrid Gel is applied to the burn wound at a dose of 2g or 5g NexoBrid sterile powder mixed with 20g or 50g sterile Gel Vehicle per 180cm\^2 of TBSA for four hours. NexoBrid: NexoBrid is an enzymatic debriding agent for Eschar Removal.	Standard of Care Non surgical and Surgical Debridement Standard of Care: Surgical or Non-Surgical methods for Eschar Removal
Overall Study STARTED	72	73
Overall Study Treated	69	70
Overall Study Number of Patients Completed 12 Month FU	66	63
Overall Study COMPLETED	66	63
Overall Study NOT COMPLETED	6	10

Reasons for withdrawal

Reasons for withdrawal
Measure	NexoBrid Gel NexoBrid Gel is applied to the burn wound at a dose of 2g or 5g NexoBrid sterile powder mixed with 20g or 50g sterile Gel Vehicle per 180cm\^2 of TBSA for four hours. NexoBrid: NexoBrid is an enzymatic debriding agent for Eschar Removal.	Standard of Care Non surgical and Surgical Debridement Standard of Care: Surgical or Non-Surgical methods for Eschar Removal
Overall Study Adverse Event	1	0
Overall Study Lost to Follow-up	2	4
Overall Study Withdrawal by Subject	1	4
Overall Study The patient was randomised but did not receive study drug treatment	2	1
Overall Study Missing	0	1

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of NexoBrid in Children With Thermal Burns Compared the Standard of Care

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NexoBrid Gel n=72 Participants NexoBrid Gel is applied to the burn wound at a dose of 2g or 5g NexoBrid sterile powder mixed with 20g or 50g sterile Gel Vehicle per 180cm\^2 of TBSA for four hours. NexoBrid: NexoBrid is an enzymatic debriding agent for Eschar Removal.	Standard of Care (SOC) n=73 Participants Non surgical and Surgical Debridement Standard of Care: Surgical or Non-Surgical methods for Eschar Removal	Total n=145 Participants Total of all reporting groups
Age, Continuous Age (years)	5.71 years STANDARD_DEVIATION 4.838 • n=5 Participants	5.83 years STANDARD_DEVIATION 4.909 • n=7 Participants	5.77 years STANDARD_DEVIATION 4.857 • n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	25 Participants n=7 Participants	55 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	48 Participants n=7 Participants	90 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	69 Participants n=5 Participants	66 Participants n=7 Participants	135 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	17 Participants n=5 Participants	16 Participants n=7 Participants	33 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	51 Participants n=5 Participants	50 Participants n=7 Participants	101 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Body Mass Index (BMI)	16.88 kg/m^2 STANDARD_DEVIATION 4.368 • n=5 Participants	17.09 kg/m^2 STANDARD_DEVIATION 4.108 • n=7 Participants	16.99 kg/m^2 STANDARD_DEVIATION 4.226 • n=5 Participants

PRIMARY outcome

Timeframe: From randomization date until complete eschar removal. For NexoBrid, assessed post application (post 2 h soaking) and for SOC assessed immediately post last dressing change for non-surgical SOC arm and immediately post excision for surgical SOC arm.

Population: All patients who were randomised into the study.

Outcome measures

Outcome measures
Measure	NexoBrid Gel n=72 Participants NexoBrid Gel is applied to the burn wound at a dose of 2g or 5g NexoBrid sterile powder mixed with 20g or 50g sterile Gel Vehicle per 180cm\^2 of TBSA for four hours. NexoBrid: NexoBrid is an enzymatic debriding agent for Eschar Removal.	Standard of Care n=73 Participants Non surgical and Surgical Debridement Standard of Care: Surgical or Non-Surgical methods for Eschar Removal
Time to Complete Eschar Removal (in Days)	0.99 Days Interval 0.88 to 1.4	5.99 Days Interval 2.71 to 9.84

SECONDARY outcome

Timeframe: Until complete eschar removal has been achieved. Complete eschar removal was achieved within 0.99 days (95% CI: 0.88 to 1.04) for the NexoBrid treatment arm and 5.99 days (95% CI: 2.71 to9.84) for the SOC treatment arm.

Population: Incidence Rate = The proportion and number of patients who required surgical excision for eschar removal.

Number of patients who needed surgical excision for eschar removal

Outcome measures

Outcome measures
Measure	NexoBrid Gel n=72 Participants NexoBrid Gel is applied to the burn wound at a dose of 2g or 5g NexoBrid sterile powder mixed with 20g or 50g sterile Gel Vehicle per 180cm\^2 of TBSA for four hours. NexoBrid: NexoBrid is an enzymatic debriding agent for Eschar Removal.	Standard of Care n=73 Participants Non surgical and Surgical Debridement Standard of Care: Surgical or Non-Surgical methods for Eschar Removal
Incidence of Surgical Excision Performed for Eschar Removal	6 Participants	47 Participants

SECONDARY outcome

Timeframe: Hematocrit - immediately before each procedure and 4 hrs after its completion. The amount of blood transfused will be summed over all transfusions carried out during the debridement procedure and up to 24 hrs from the end time of the debridement procedure

Population: Full analysis set (FAS): 145 patients

Measured by actual blood loss \[ABL\]. Actual blood loss was the calculated blood loss summed over all procedures carried out to remove eschar, using hematocrit values measured immediately before each procedure and 4 hours after its completion and the amount of blood transfused was summed over all transfusions carried out during the debridement procedure and up to 24 hours from the end time of the debridement procedure.

Outcome measures

Outcome measures
Measure	NexoBrid Gel n=72 Participants NexoBrid Gel is applied to the burn wound at a dose of 2g or 5g NexoBrid sterile powder mixed with 20g or 50g sterile Gel Vehicle per 180cm\^2 of TBSA for four hours. NexoBrid: NexoBrid is an enzymatic debriding agent for Eschar Removal.	Standard of Care n=73 Participants Non surgical and Surgical Debridement Standard of Care: Surgical or Non-Surgical methods for Eschar Removal
Blood Loss Related to Eschar Removal	32.26 mL Standard Deviation 284.757	202.55 mL Standard Deviation 409.147

SECONDARY outcome

Timeframe: Assessment will be performed by the investigator immediately after each autograft procedure was performed, before application of coverage.

Population: FAS, Patients with at least one DPT target wound.

Percent area of deep partial thickness wounds autografted

Outcome measures

Outcome measures
Measure	NexoBrid Gel n=60 Participants NexoBrid Gel is applied to the burn wound at a dose of 2g or 5g NexoBrid sterile powder mixed with 20g or 50g sterile Gel Vehicle per 180cm\^2 of TBSA for four hours. NexoBrid: NexoBrid is an enzymatic debriding agent for Eschar Removal.	Standard of Care n=55 Participants Non surgical and Surgical Debridement Standard of Care: Surgical or Non-Surgical methods for Eschar Removal
Percent Area of Autograft Performed in DPT Wounds - Main Analysis, Patient Level.	15.9 percent Standard Deviation 38.57	22.8 percent Standard Deviation 43.72

SECONDARY outcome

Timeframe: Patient's wounds were assessed until complete healing of all wounds, during the period from complete eschar removal was achieved until complete wound closure. Median time in the population was approx. 4.5 weeks and longest follow up period was of 12 weeks

Population: Main Analysis, Target Wound Level, Deep Partial Thickness Target Wounds Only

Number of autografts performed in deep partial thickness wounds

Outcome measures

Outcome measures
Measure	NexoBrid Gel n=81 Deep Partial Thickness Wounds NexoBrid Gel is applied to the burn wound at a dose of 2g or 5g NexoBrid sterile powder mixed with 20g or 50g sterile Gel Vehicle per 180cm\^2 of TBSA for four hours. NexoBrid: NexoBrid is an enzymatic debriding agent for Eschar Removal.	Standard of Care n=69 Deep Partial Thickness Wounds Non surgical and Surgical Debridement Standard of Care: Surgical or Non-Surgical methods for Eschar Removal
Incidence of Autograft Performed in Deep Partial Thickness Wounds	21 autographs performed	26 autographs performed

Adverse Events

NexoBrid Gel

Serious events: 2 serious events

Other events: 31 other events

Deaths: 0 deaths

Standard of Care

Serious events: 6 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	NexoBrid Gel n=69 participants at risk NexoBrid Gel is applied to the burn wound at a dose of 2g or 5g NexoBrid sterile powder mixed with 20g or 50g sterile Gel Vehicle per 180cm\^2 of TBSA for four hours. NexoBrid: NexoBrid is an enzymatic debriding agent for Eschar Removal.	Standard of Care n=70 participants at risk Non surgical and Surgical Debridement Standard of Care: Surgical or Non-Surgical methods for Eschar Removal
Cardiac disorders Tachycardia	1.4% 1/69 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.	0.00% 0/70 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.
Gastrointestinal disorders Pyrexia	1.4% 1/69 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.	0.00% 0/70 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.
Gastrointestinal disorders Systemic Inflammatory Response Syndrome	1.4% 1/69 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.	0.00% 0/70 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.
General disorders Withdrawal Syndrome	0.00% 0/69 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.	1.4% 1/70 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.
Infections and infestations Viral Infection	0.00% 0/69 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.	1.4% 1/70 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.
Injury, poisoning and procedural complications Concussion	0.00% 0/69 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.	1.4% 1/70 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.
Injury, poisoning and procedural complications Injury	0.00% 0/69 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.	2.9% 2/70 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.
Injury, poisoning and procedural complications Procedural Pain	0.00% 0/69 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.	1.4% 1/70 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.
Injury, poisoning and procedural complications Wound Complication	0.00% 0/69 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.	1.4% 1/70 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.
Musculoskeletal and connective tissue disorders Joint Contracture	1.4% 1/69 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.	0.00% 0/70 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.
Respiratory, thoracic and mediastinal disorders Laryngospasm	0.00% 0/69 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.	1.4% 1/70 • Time of informed consented until subject's study completion (12 months post wound closure) or earlier if early termination from study. An adverse event is an undesirable or unintentional event that occurs during use of the study Drug, whether or not considered related to the Drug; this includes clinically significant changes in laboratory values and therapeutic failures. Regardless of the severity or relationship to the investigational Drug, all adverse events occurring during the study period should be recorded in a subject's CRFs.

Other adverse events

Additional Information

Keren David Zarbiv

MediWound

Phone: 972-77-9714103

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place